Safety of and Immune Response to Two Different HIV Vaccines, Each Followed by a Adenoviral Vaccine Boost, in HIV Uninfected Adults

NCT00270218 | Completed Phase 1

• 2 other identifiers: HVTN 06810060
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine the safety of and immune response to an adenoviral vector HIV vaccine or a DNA HIV vaccine, each followed by an adenoviral vector HIV vaccine boost, in HIV uninfected adults.

Conditions

HIV Infections

Keywords

HIV Seronegativity; Adenoviral Vector Vaccine; DNA Plasmid Vaccine

Outcome Measures

Primary Outcomes (3)

• Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences)

  After each injection and for 6 months after the last injection

• Magnitude of HIV-specific CD4+ and CD8+ T-cell responses, defined as percentage of T cells expressing IFN-gamma or IL-2 to vaccine peptide pools

  Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination

• Social impact (negative experiences or problems associated with participation in the study and other social, travel, work, school, health care, life insurance, health insurance, housing, military, or other impacts identified by the participant)

  Throughout the study

Secondary Outcomes (3)

• Expression of HIV-specific T-cell memory differentiation markers and other markers of interest by flow cytometry

  Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination

• Titer to HIV-specific binding antibodies assessed by ELISA

  Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination

• Titer of HIV-specific neutralization antibodies assessed by neutralizing antibody assay, if indicated

  Within first 6 weeks following primary adenoviral vaccination, the second DNA vaccination, and the booster adenoviral vaccination

Study Arms (4)

1

EXPERIMENTAL

Arm 1 participants will be given an injection of VRC-HIVADV014-00-VP vaccine on Days 0 and 168.

Biological: VRC-HIVADV014-00-VP

2

PLACEBO COMPARATOR

Arm 2 participants will be given an injection of final formulation buffer (FFB) on Days 0 and 168.

Biological: FFB

3

EXPERIMENTAL

Arm 3 participants will be given an injection of VRC-HIVDNA009-00-VP vaccine on Days 0 and 28. Participants will also be given an injection of VRC-HIVADV014-00-VP on Day 168.

Biological: VRC-HIVADV014-00-VP; Biological: VRC-HIVDNA009-00-VP

4

PLACEBO COMPARATOR

Arm 4 participants will be given an injection of phosphate buffered saline (PBS) on Days 0 and 28 and an injection of FFB on Day 168.

Biological: FFB; Biological: PBS

Interventions

VRC-HIVADV014-00-VP BIOLOGICAL

HIV-1 recombinant adenoviral vector vaccine given as a 1 mL intramuscular injection in the deltoid

1; 3

VRC-HIVDNA009-00-VP BIOLOGICAL

HIV-1 DNA plasmid vaccine given as a 1 mL intramuscular injection in the deltoid

3

FFB BIOLOGICAL

Adenoviral vector FFB given as a 1 mL intramuscular injection in the deltoid

2; 4

PBS BIOLOGICAL

phosphate buffered saline

4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV uninfected
• Good general health
• Pre-existing adenovirus 5 (Ad5) neutralizing antibody titers of less than a 1:12 ratio
• Hepatitis B surface antigen negative
• Anti-hepatitis C virus (anti-HCV) antibody negative or negative HCV PCR if anti-HCV antibody is positive
• Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed during the study
• Willing to receive HIV test results
• Understand the vaccination procedure
• Willing to use acceptable forms of contraception

You may not qualify if:

• HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
• Immunosuppressive medications within 168 days prior to first study vaccination
• Blood products within 120 days prior to first study vaccination
• Live attenuated vaccines within 30 days prior to first study vaccination
• Investigational research agents within 30 days prior to first study vaccination
• Medically indicated subunit or killed vaccines within 14 days prior to first study vaccination
• Current anti-tuberculosis (TB) preventive therapy or treatment
• Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
• Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
• Any job-related responsibility that would interfere with the study
• Serious adverse reactions to vaccines, including hypersensitivity and related symptoms. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
• Autoimmune disease or immunodeficiency
• Active syphilis infection. Participants who have been fully treated for syphilis for more than 6 months prior to study entry are not excluded.
• Moderate to severe asthma. More information on this criterion can be found in the protocol.
• Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

Alabama Vaccine CRS

Birmingham, Alabama, 35294-2041, United States

Location

San Francisco Vaccine and Prevention CRS

San Francisco, California, 94102, United States

Location

NY Blood Ctr./Union Square CRS

New York, New York, 10003, United States

Location

HIV Prevention & Treatment CRS

New York, New York, 10032, United States

Location

Univ. of Rochester HVTN CRS

Rochester, New York, 14642-0001, United States

Location

Vanderbilt Vaccine CRS

Nashville, Tennessee, 37232, United States

Location

FHCRC/UW Vaccine CRS

Seattle, Washington, 98104, United States

Location

Related Publications (5)

• Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.

  PMID: 15761255 BACKGROUND

• De Rosa SC, Lu FX, Yu J, Perfetto SP, Falloon J, Moser S, Evans TG, Koup R, Miller CJ, Roederer M. Vaccination in humans generates broad T cell cytokine responses. J Immunol. 2004 Nov 1;173(9):5372-80. doi: 10.4049/jimmunol.173.9.5372.

  PMID: 15494483 BACKGROUND

• Shiver JW, Emini EA. Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004;55:355-72. doi: 10.1146/annurev.med.55.091902.104344.

  PMID: 14746526 BACKGROUND

• Vanniasinkam T, Ertl HC. Adenoviral gene delivery for HIV-1 vaccination. Curr Gene Ther. 2005 Apr;5(2):203-12. doi: 10.2174/1566523053544236.

  PMID: 15853728 BACKGROUND

• Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.

  PMID: 25820067 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Stephen De Rosa, MD

  Fred Hutchinson Cancer Research Center and University of Washington

  STUDY CHAIR

• Spyros A. Kalams, MD

  Vanderbilt University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2005
• First Posted: December 26, 2005
• Study Start: February 1, 2006
• Study Completion: August 1, 2007
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

US (7)